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Introduction: Prostate cancer and its treatment, particularly androgen deprivation therapy (ADT), can profoundly impact patients' quality of life. The aim of the prospective observational study reported here was to evaluate the effects of ADT on various aspects of quality of life in men with prostate cancer at a community-based hospital in Southern Italy., Methods: Eligible men initiating hormonal therapy were recruited between December 2021 and December 2023. Data were collected at baseline (T 0 ) and after 3 months (T 1 ) and 6 months (T 2 ) of ADT using standardized questionnaires (European Organization for Research and Treatment of Cancer [EORTC] QLQ-C30, EORTC QLQ-PR25) and semi-structured interviews., Results: Of the 52 participants, 43 completed all three assessments. The EORTC QLQ-C30 showed a statistically significant worsening in physical functioning (mean score decrease from 83.8 at T 0 to 76.7 at T 2 ; p < 0.001), increased fatigue (from 23.7 to 35.2; p < 0.001), and insomnia (from 23.7 to 31.8; p = 0.048) following ADT initiation. The QLQ-PR25 revealed a significant decline in sexual functioning (from 59 to 26.9; p < 0.001) and sexual activity (from 27.3 to 12; p = 0.001). Interviews revealed a significant rise in the number of patients reporting depressed mood. Interviews also highlighted a worsening in body image perception and sexuality, increased feelings of dependence, and challenges in the social and relational spheres., Conclusions: ADT significantly impacts various aspects of quality of life in men with prostate cancer, particularly physical functioning, fatigue, sexual function, body image, and emotional well-being. These results underscore the critical importance of a comprehensive, patient-centered approach that addresses both the physical and psychosocial aspects of care., Competing Interests: Declarations Conflict of Interest Francesca Cappuccio, Carlo Buonerba, Luca Scafuri, Rossella Di Trolio, Pasquale Dolce, Serena Orsola Trabucco, Filomena Erbetta, Elvira Tulimieri, Antonella Sciscio, Concetta Ingenito and Antonio Verde have nothing to disclose. Giuseppe Di Lorenzo is an Editorial Board member of Oncology and Therapy. He was not involved in the selection of peer reviewers for the manuscript nor any of the subsequent editorial decisions. Ethical Approval The study was approved by the Ethics Committee (“Comitato Etico Campania Centro”; approval/ protocol number 1945). The research was conducted in accordance with the Declaration of Helsinki. All patients provided written informed consent. Permission was received by the EORTC Quality of Life Group to use the questionnaires., (© 2024. The Author(s).)

Bladder cancer, which has a rising incidence, is the 10th most common cancer. The transitional cell carcinoma histotype is aggressive and often current therapies are ineffective. We investigated the anti-proliferative effect of quercetin, a natural flavonoid, in combination with the alkylating agent mafosfamide (MFA) on two human bladder cancer cell lines, namely RT112 and J82, representing the progression from low-grade to high-grade tumors, respectively. In both cell types, the combined treatment led to a synergic reduction in cell viability confirmed by a combination index of less than one, though different biological responses were noted. In J82 cells, MFA alone and, to a lesser extent, with quercetin caused cell cycle arrest in the G2/M phase, but only the combined treatment triggered apoptotic cell death. In contrast, in RT112 cells, quercetin induced autophagy, evidenced by the autophagosome formation and the increase in LC-3 lipidation. Interestingly, the synergistic effect was observed only when cells were pre-treated with MFA for 24 h before adding quercetin, not in the reverse order. This suggests that quercetin may help overcome MFA resistance to apoptosis. Although further studies are needed, investigating the combined effects of quercetin and MFA could help elucidate the mechanisms of drug resistance in bladder cancer treatment.

Background: Oxidative stress has emerged as a key contributor to numerous NCDs (non-communicable diseases), including cardiovascular diseases, cancer, and diabetes. This study aims to explore the potential of targeted interventions to mitigate oxidative stress as part of a primary prevention strategy., Methods: The study included 32 healthy participants (11 men, 21 women) aged 45-65 who completed both the initial and follow-up assessments of the Healthy Days Initiative, a community-based wellness program organized by the non-profit Associazione O.R.A. ETS. Through blood analysis, vital sign assessment, lifestyle questionnaires, and individualized recommendations, participants received guidance on improving their health and reducing disease risk. The initiative also offered the opportunity for participants to consume a flavonoid supplement containing quercitrin, rutin, and hesperidin, with the goal of reducing oxidative stress. Participants who opted for supplementation were instructed to take 1-2 tablets daily for two weeks. Data collected included demographic information, anthropometric measurements, vital signs, dietary and lifestyle habits, medical history, WHO-5 Well-Being Index scores, and blood parameters., Results: Significant reductions were observed in glucose levels (from 82 to 74.5 mg/dL), reactive oxygen metabolites (d-ROMs) (from 394.5 to 365.5 U.CARR), and systolic blood pressure (from 133 to 122 mmHg) after the two-week flavonoid intervention. Most participants (26/31) reported no side effects, and the majority (30/31) expressed a willingness to continue using a product combination of quercitrin, rutin, and hesperidin or a similar product long-term., Conclusions: While limited in scope and duration, the PREVES-FLAVON study contributes valuable insights to the growing body of evidence suggesting that flavonoid supplementation may play a significant role in reducing risk factors associated with NCDs in primary prevention settings. By targeting novel risk factors such as oxidative stress, this intervention holds promise for mitigating the global burden of NCDs and promoting healthy aging.

Background: The last years have seen unprecedented improvement in breast cancer (BC) survival rates. However, this entirely apply to female BC patients, since gender minorities (male, transgender/gender-diverse) are neglected in BC phase III registration clinical trials., Methods: We conducted a scoping review of phase III clinical trials of agents with a current positioning within the therapeutic algorithms of BC., Results: We selected 51 phase III trials. Men enrollment was allowed in 35.3% of trials. In none of the trial inclusion/exclusion criteria referred to transgender/gender-diverse people. A numerical higher rate of enrolled men was observed in the contemporary as compared to historical group. We found a statistically significant association between the drug class and the possibility of including men: 100%, 80%, 50%, 33.3%, 25%, 10% and 9.1% of trials testing ICI/PARP-i, ADCs, PI3K/AKT/mTOR-i, anti-HER2 therapy, CDK4/6-i, ET alone, and CT alone. Overall, 77409 patients were enrolled, including 112 men (0.2%). None of the trial reported transgender/gender-diverse people proportion. Studies investigating PARP-i were significantly associated with the highest rate of enrolled men (1.42%), while the lowest rates were observed for trials of CT (0.13%), ET alone (0.10%), and CDK 4/6-I (0.08%), p < 0.001., Conclusions: We confirmed that gender minorities are severely underrepresented among BC registration trials. We observed a lower rate of men in trials envisaging endocrine manipulation or in less contemporary trials. This work sought to urge the scientific community to increase the awareness level towards the issue of gender minorities and to endorse more inclusive criteria in clinical trials., Competing Interests: Declaration of competing interest FM reports personal fees from Roche, Novartis, Pfizer, Seagen, Gilead, Astrazeneca, Lilly, Menarini all outside the submitted work (all the disclosed activities are outside the submitted work). CDA reports advisory role for Roche, Lilly, Novartis, Astrazeneca, Pfizer, Seagen, Daiichi-Sankyo, Gilead, and GSK and speaker honoraria from Roche, Lilly, Novartis, Pfizer, Seagen, GSK, GILEAD, and Daiichi-Sankyo; travel Grants from Gilead and research support (to the Institution) from Novartis, GILEAD, and Daiichi-Sankyo outside the submitted work (all the disclosed activities are outside the submitted work). RC reports fees for talk or consultation from Novartis, Lilly, MSD, Gilead, Roche, Pfizer, Veracyte, Seagen, Astra Zeneca, Daichii Sankyo, Menarini, Pierre-Fabre (all the disclosed activities are outside the submitted work). EB has received grants or contracts from Astra-Zeneca, Roche and honoraria for lectures from Merck-Sharp & Dome, Astra-Zeneca, Pfizer, Eli-Lilly, Bristol-Myers Squibb, Novartis, Takeda and Roche; he has been member of Data Safety Monitoring Board or Advisory Board of Merck-Sharp & Dome, Pfizer, Novartis, Bristol-Myers Squibb, Astra-Zeneca, and Roche (all the disclosed activities are outside the submitted work). AV reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: AndromedaE20, Oncotech; support for attending meetings and/or travel: Pierre Fabre, Lilly, Gilead, Seagen, Novartis, MSD, Menarini (all the disclosed activities are outside the submitted work). LDM reports institutional grants from Eli Lilly, Novartis, Roche, Daiichi Sankyo, Seagen, Astrazeneca, Gilead, Pierre Fabre; consulting fees: Eli Lilly, Gilead, Daiichi Sankyio; payment or honoraria for lectures, presentations, speakers bureaus: Roche, Novartis, Pfizer, Eli Lilly, Astrazeneca, MSD, Seagen, Gilead, Pierre Fabre, Eisai, Exact Sciences, Ipsen, GSK, Agendia, Stemline; support for attending meetings and/or travel: Roche, Pfizer, Eisai, Daiichi Sankyo, Astrazeneca, Gilead; Participation on a Data Safety Monitoring Board or Advisory Board: Novartis, Roche, Eli Lilly, Pfizer, Daiichi Sakyo, Exact Sciences, Gilead, Pierre Fabre, Eisai, Astrazeneca, Agendia, GSK, Seagen, Olema, MSD, Stemline Menarini (all the disclosed activities are outside the submitted work). FM reports consultancy fees from Roche, Novartis, AstraZeneca, Daiichy Sankyo, SeaGen, MSD, Eli Lilly, Pfizer, and Pierre Fabre, and Travel Grants from Roche and Astra Zeneca; from May 15th, 2023, FM is Roche employee (all the disclosed activities are outside the submitted work). VG reports personal fees for advisory board membership for AstraZeneca, Daiichi Sankyo, Eisai, Eli Lilly, Exact Sciences, Gilead, Merck Serono, MSD, Novartis, Pfizer, Olema Oncology, Pierre Fabre; personal fees as an invited speaker for AstraZeneca, Daiichi Sankyo, Eli Lilly, Exact Sciences, Gilead, GSK, Novartis, Roche and Zentiva; personal fees for expert testimony for Eli Lilly. All the remaining authors have no conflict of interest to report., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: This retrospective study investigates the efficacy of cemiplimab, a monoclonal antibody targeting the PD-1 receptor, in treating squamous cell carcinoma (SCC) of the skin., Methods: The study analyzes data from 50 patients with SCC, focusing on various clinical parameters, including patient demographics, tumor characteristics, treatment history, disease status at the beginning of therapy, and survival outcomes., Results: Of the patients who received at least one cycle of cemiplimab, 42% showed a clinical response. Adverse reactions were generally low, with the safety profile deemed excellent. During a median follow-up of 9.6 months, 17 patients experienced progression or death. Among these, 15 patients had died at the time of the analysis. The median progression-free survival (PFS) for the entire cohort was approximately 20.8 months, while median overall survival (OS) was not reached. Univariate Cox regression analysis for PFS showed that tumors in the arms and legs were associated with higher progression risk, while age above 65 years was not statistically significant. Distant metastasis exhibited a trend towards improved PFS. In terms of OS, distant metastasis was a significant predictor of reduced survival, while age above 65 years was not statistically significant. In a multivariate model, only the absence of distant metastasis remained significant, with an adjusted odds ratio (OR) of 12.3 (95% confidence interval 1.3-112.1)., Conclusion: These findings provide valuable insights into the real-world effectiveness of cemiplimab in SCC management., (© 2023. The Author(s).)

Background: In patients affected by high-risk nonmuscle invasive bladder cancer (HR-NMIBC) progression to muscle invasive status is considered as the main indicator of local treatment failure. We aimed to investigate the effect of progression and time to progression on overall survival (OS) and to investigate their validity as surrogate endpoints., Methods: A total of 1,510 patients from 18 different institutions treated for T1 high grade NMIBC, followed by a secondary transurethral resection and BCG intravesical instillation. We relied on random survival forest (RSF) to rank covariates based on OS prediction. Cox's regression models were used to quantify the effect of covariates on mortality., Results: During a median follow-up of 49.0 months, 485 (32.1%) patients progressed to MIBC, while 163 (10.8%) patients died. The median time to progression was 82 (95%CI: 78.0-93.0) months. In RSF time-to-progression and age were the most predictive covariates of OS. The survival tree defined 5 groups of risk. In multivariable Cox's regression models accounting for progression status as time-dependent covariate, shorter time to progression (as continuous covariate) was associated with longer OS (HR: 9.0, 95%CI: 3.0-6.7; P < 0.001). Virtually same results after time to progression stratification (time to progression ≥10.5 months as reference)., Conclusion: Time to progression is the main predictor of OS in patients with high risk NMIBC treated with BCG and might be considered a coprimary endpoint. In addition, models including time to progression could be considered for patients' stratification in clinical practice and at the time of clinical trials design., Competing Interests: Declaration of competing interest Each of the authors certify that the manuscript represents original and valid work that has not been previously published and is not currently under consideration by any other journal. Additionally, all the authors: have given final approval of the submitted manuscript approved the contents of this paper and have participated sufficiently in the work to take public responsibility for all content. None of the contributing authors have any conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript. No funding or other financial support was received., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background and Objectives: To investigate the role of preoperative albumin-to-alkaline phosphatase ratio (AAPR) in predicting pathologic node-positive (pN+) disease in penile cancer (PC) patients undergoing inguinal lymph node dissection (ILND). Materials and Methods : Clinical data of patients with squamous cell carcinoma (SCC) PC + ILND at a single high-volume institution between 2016 and 2021 were collected and retrospectively analyzed. An AAPR was obtained from preoperative blood analyses performed within 30 days from their scheduled surgery. A ROC curve analysis was used to assess AAPR cutoff, in addition to the Youden Index. Logistic regression analysis was utilized for an odds ratio (OR), 95% confidence interval (CI) calculations, and an estimate of pN+ disease. A p value < 0.05 was considered to be as statistically significant. Results : Overall, 42 PC patients were included in the study, with a mean age of 63.6 ± 12.9 years. The AAPR cut-off point value was determined to be 0.53. The ROC curve analysis reported an AUC of 0.698. On multivariable logistic regression analysis lymphovascular invasion (OR = 5.38; 95% CI: 1.47-9.93, p = 0.022), clinical node-positive disease (OR = 13.68; 95% CI: 4.37-43.90, p < 0.009), and albumin-to-alkaline phosphatase ratio ≤ 0.53 (OR = 3.61; 95% CI: 1.23-12.71, p = 0.032) were predictors of pN+ involvement. Conclusions : Preoperative AAPR may be a potentially valuable prognostic marker of pN+ disease in patients who underwent surgery for PC.

Introduction: Several programmed death ligand-1 (PD1/L1) immune checkpoint inhibitors (ICIs) are approved in urothelial carcinoma (UC)., Patients and Methods: To address the need for predictors of the efficacy of ICIs in metastatic urothelial carcinoma (mUC), randomized controlled trials of PD1/L1 inhibitors alone or in combination with chemotherapy in this patient population were systematically reviewed, and differences in ICI-associated survival outcomes according to available baseline variables were quantitatively assessed., Results: The quantitative analysis included 6524 patients with mUC. No visceral metastatic site (HR 0.67; 95% CI, 0.76-0.90) and high PDL-1 expression (HR 0.74; 95% CI, 0.640.87) were significantly associated with a reduced risk of death., Conclusion: Treatment with an ICI-containing regimen was associated with a reduced risk of death in mUC patients, which was associated with PDL-1 expression and metastatic site. Further research is warranted., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Anti-VEGF (vascular endothelial growth factor) agents were associated with increased risk of several cardiovascular events, while one meta-analysis did not show any significantly increased risk of cardiotoxicity associated with the use of immune checkpoint inhibitors (ICIs). This meta-analysis of randomized-controlled trials (RCTs) was designed to compare cardiovascular toxicity of anti-VEGF agents plus ICI vs anti-VEGF agents without ICIs. A systematic search of the literature was conducted to include all full papers reporting about phase II and III randomized controlled trials (RCTs) conducted in patients with solid malignancies randomized to an anti-VEGF agent plus an ICI vs. an anti-VEGF agent without an ICI. Overall incidences of cardiovascular events were compared between these two treatment groups estimating the corresponding odds ratios. This analysis suggests that ICIs may increase the risk of cardiovascular toxicities associated with anti-VEGF therapies. Further research, including real world studies, is warranted., Competing Interests: Declaration of Competing Interest, (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: Approximately a third of cancer-related deaths are attributable to modifiable factors., Methods: As a pilot experience, a cross-sectional survey was conducted in 8,000 citizens residing in four different municipalities of the Salerno province (Sarno, Pagani, San Valentino Torio, and San Marzano sul Sarno) to investigate key lifestyle and dietary habits., Results: A total of 703 of participants (8.7%) reported a history of malignancy. Alarmingly, 30.5% declared to be a current smoker, while 78.8% did not report any kind of physical activity. Encouragingly, 64.5% declared to be abstemious, and 83.0% declared to consume fruit and vegetables every day, while 4.7% and 31.9% declared not to consume meat and fried food, respectively, at any time. Never-consumers of fruit and vegetables had higher odds of having a history of colorectal cancer (OR = 5.01; 95% CI = 1.46-17.15; p = 0.01)., Conclusions: The PREVES study has served to prove the validity of an operational model allowing to integrate hospital and territorial healthcare services, which we expect to be applied at a larger scale. Key information regarding dietary and lifestyle habits of the investigated population was obtained. Larger studies conducted using more accurate approaches to investigate diet, such as 24-h recalls and food frequency questionnaires, are warranted., (© 2023 S. Karger AG, Basel.)

Introduction: The benefit of neoadjuvant systemic therapy (NAST) is not yet supported by randomized controlled trials in upper tract urothelial carcinoma (UTUC), but the evidence is increasing. This narrative systematic review was conducted to evaluate the available evidence on the role of NAST in patients undergoing radical nephroureterectomy (RNU) for UTUC., Evidence Acquisition: We searched for all relevant articles or conference abstracts published and indexed in PubMed, Embase, and Scopus on July 19, 2021. The study was reported according to the PRISMA criteria and designed within the PICOS framework. We included studies comparing patients with non-metastatic UTUC who received neoadjuvant chemotherapy (NAC) or immunotherapy (NAI) with patients who underwent definitive surgery alone or surgery plus adjuvant systemic therapy. Prospective uncontrolled studies were also included., Evidence Synthesis: We identified 27 reports (NAC, N.=24 and NAI, N.=3) published between 2010 and 2021. Twenty of the 24 studies on NAC were retrospective comparative analyses, whereas the remaining four were prospective single-arm studies. One of the three NAI studies exclusively enrolled patients with UTUC. NAC was associated with improved survival and better pathological response relative to surgery alone, but there was no clear advantage when compared to surgery plus adjuvant chemotherapy. Overall, the drug-induced toxicity and risk of disease progression were acceptable but the inherent bias across study designs, inadequate reporting and heterogeneous definition of primary outcomes render it difficult to synthesize results, compare centers, and inform practice., Conclusions: The current level of evidence supporting NAST for UTUC is relatively low and the inability to predict responsiveness and thereby pinpoint the optimal candidates remains a major challenge. There is a need to compare NAST to adjuvant therapies using clearly defined primary endpoints as minimum reporting standards developed by a multidisciplinary team.

Purpose: Emerging evidence suggest that infection-dependent hyperactivation of complement system (CS) may worsen COVID-19 outcome. We investigated the role of predicted high impact rare variants - referred as qualifying variants (QVs) - of CS genes in predisposing asymptomatic COVID-19 in elderly individuals, known to be more susceptible to severe disease., Methods: Exploiting exome sequencing data and 56 CS genes, we performed a gene-based collapsing test between 164 asymptomatic subjects (aged ≥60 years) and 56,885 European individuals from the Genome Aggregation Database. We replicated this test comparing the same asymptomatic individuals with 147 hospitalized patients with COVID-19., Results: We found an enrichment of QVs in 3 genes (MASP1, COLEC11, and COLEC10), which belong to the lectin pathway, in the asymptomatic cohort. Analyses of complement activity in serum showed decreased activity of lectin pathway in asymptomatic individuals with QVs. Finally, we found allelic variants associated with asymptomatic COVID-19 phenotype and with a decreased expression of MASP1, COLEC11, and COLEC10 in lung tissue., Conclusion: This study suggests that genetic rare variants can protect from severe COVID-19 by mitigating the activity of lectin pathway and prothrombin. The genetic data obtained through ES of 786 asymptomatic and 147 hospitalized individuals are publicly available at http://espocovid.ceinge.unina.it/., Competing Interests: Conflict of Interest The authors declare no conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

The aim of the present study is to assess saliva as a reliable specimen for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection by real-time reverse transcription-PCR (RT-PCR), especially in community mass screening programs. The performance analysis considered 1,221 total samples [nasopharyngeal (NP) swabs and corresponding saliva], tested by means of a reference diagnostic real-time RT-PCR assay. Conflicting results were further investigated with a second, more sensitive, reference assay. Analysis of agreement showed a good concordance (95.82%), with a k coefficient value of.74 ( p < 0.001); moreover, a follow-up analysis revealed the presence of viral gene targets in saliva samples at the time point the corresponding NP swabs turned negative. Data obtained prove the reliability of this alternative biofluid for SARS-CoV-2 detection in real-time RT-PCR. Considering the role of saliva in the coronavirus disease 2019 (COVID-19) transmission and pathogenesis, and the advantages in the use of salivary diagnostics, the present validation supports the use of saliva as an optimal choice in large-scale population screening and monitoring of the SARS-CoV-2 virus., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pierri, Tafuro, Cuomo, Concilio, Vassallo, Pierri, Ferro, Rofrano, Gallo, Stasio, Mancusi, Galdi, Coppola, Buonerba, Atripaldi and Cerino.)

Bladder cancer is the most common malignancy of the urinary tract. Cystoscopy represents the gold standard in the diagnosis of suspicious bladder lesions. However, the procedure is invasive and burdened by pain, discomfort and infective complications. Cytology, which represents an alternative diagnostic possibility is limited by poor sensitivity. Considering the limitations of both procedures, and the necessity to perform multiple evaluations in patients who are in follow-up for bladder cancer, an improved non-invasive methodology is required in the clinical management of this disease. Liquid biopsy, e.g. the detection of clinical biomarkers in urine, represent a promising novel and non-invasive approach that could overcome those limitations and be integrated into the current clinical practice. The aim of this review is to summarize the state of the art of this approach and the latest novelties regarding detection, prognosis and surveillance of bladder cancer., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Colorectal cancer (CRC) is a high incidence disease, characterized by high morbidity and mortality rates. Early diagnosis remains challenging because fecal occult blood screening tests have performed sub-optimally, especially due to hemorrhoidal, inflammatory, and vascular diseases, while colonoscopy is invasive and requires a medical setting to be performed. The objective of the present study was to determine if serum metabolomic profiles could be used to develop a novel screening approach for colorectal cancer. Furthermore, the study evaluated the metabolic alterations associated with the disease. Untargeted serum metabolomic profiles were collected from 100 CRC subjects, 50 healthy controls, and 50 individuals with benign colorectal disease. Different machine learning models, as well as an ensemble model based on a voting scheme, were built to discern CRC patients from CTRLs. The ensemble model correctly classified all CRC and CTRL subjects (accuracy = 100%) using a random subset of the cohort as a test set. Relevant metabolites were examined in a metabolite-set enrichment analysis, revealing differences in patients and controls primarily associated with cell glucose metabolism. These results support a potential use of the metabolomic signature as a non-invasive screening tool for CRC. Moreover, metabolic pathway analysis can provide valuable information to enhance understanding of the pathophysiological mechanisms underlying cancer. Further studies with larger cohorts, including blind trials, could potentially validate the reported results.

Introduction: Cancer aggravates COVID-19 prognosis. Nosocomial transmission of SARS-CoV-2 is particularly frequent in cancer patients, who need to attend hospitals regularly. Since March 2020, all cancer patients having access to the Oncology Unit at the "Andrea Tortora" Hospital (Pagani, Salerno - referred to as "the Hospital") as inpatients or outpatients receiving intravenous therapy have been screened for SARS-CoV-2 using RT-PCR nasal swab. The ongoing COICA (COVID-19 infection in cancer patients) study is an ambispective, multicenter, observational study designed to assess the prognosis of SARS-CoV-2 infection in cancer patients. The aim of the study presented here was to explore potential differences in COVID-19-related outcomes among screening-detected versus nonscreening-detected SARS-CoV-2-infected patients. Methods: The COICA study enrolled cancer patients who had received any anticancer systemic therapy within 3 months since the day they tested positive for SARS-CoV-2 on RT-PCR. The target accrual is 128 patients, and the study was approved by the competent Ethics Committee. Only the subgroup of patients enrolled at the Hospital was considered in this unplanned interim analysis. Logistic regression analysis was used to evaluate the association of screening-based versus nonscreening-based diagnosis. Results: Since March 15, 2020, until August 15, 2021, a total of 931 outpatients and 230 inpatients were repeatedly screened for SARS-CoV-2 using RT-PCR nasal swab at the Hospital. Among these, 71 asymptomatic patients were positive on routine screening and 5 patients were positive for SARS-CoV-2 outside the institutional screening. Seven patients died because of COVID-19. At univariate analysis, nonscreening- versus screening-detected SARS-CoV-2 infection was associated with significantly higher odds of O 2 therapy (OR = 16.2; 95% CI = 2.2-117.1; p = 0.006), hospital admission (OR = 31.5; 95% CI = 3.1-317.8; p = 0.003), admission to ICU (OR = 23.0; 95% CI = 2.4-223.8; p = 0.007), and death (OR = 8.8; 95% CI = 1.2-65.5; p = 0.034). Conclusion: Routine screening with RT-PCR may represent a feasible and effective strategy in reducing viral circulation and possibly COVID-19 mortality in patients with active cancer having repeated access to hospital facilities., (© 2021 S. Karger AG, Basel.)

Introduction: The association between obesity and clinically significant prostate cancer (PCa) is still a matter of debate. In this study, we evaluated the effect of body mass index (BMI) on the prediction of pathological unfavorable disease (UD), positive surgical margins (PSMs), and biochemical recurrence (BCR) in patients with clinically localized (≤cT2c) International Society of Urological Pathology (ISUP) grade group 1 PCa at biopsy., Methods: 427 patients with ISUP grade group 1 PCa who have undergone radical prostatectomy and BMI evaluation were included. The outcome of interest was the presence of UD (defined as ISUP grade group ≥3 and pT ≥3a), PSM, and BCR., Results: Statistically significant differences resulted in comparing BMI with prostate-specific antigen (PSA) and serum testosterone levels (both p < 0.0001). Patients with UD and PSM had higher BMI values (p < 0.0001 and p = 0.006, respectively). BCR-free survival was significantly decreased in patients with higher BMI values (p < 0.0001). BMI was an independent risk factor for BCR and PSM. Receiver-operating characteristic analysis testing PSA accuracy in different BMI groups, showed that PSA had a reduced predictive value (area under the curve [AUC] = 0.535; 95% confidence interval [CI] = 0.422-0.646), in obese men compared to overweight (AUC = 0.664; 95% CI = 0.598-0.725) and normal weight patients (AUC = 0.721; 95% CI = 0.660-0.777)., Conclusion: Our findings show that increased BMI is a significant predictor of UD and PSM at RP in patients with preoperative low-to intermediate-risk diseases, suggesting that BMI evaluation may be useful in a clinical setting to identify patients with favorable preoperative disease characteristics harboring high-risk PCa., (© 2021 S. Karger AG, Basel.)

Background: The evaluation of environmental exposure risk requires a global analysis of pollution phenomena, including biological effects and potentially correlated clinical outcomes in susceptible populations. Although human biomonitoring plays a fundamental role in assessing the degree of contamination, it is not effective alone in identifying a direct link between exposure, biomolecular effects and outcomes on target organisms. While toxicogenomics and epidemiology are mainly focused on the investigation of molecular reactions and clinical outcomes, the monitoring of environmental matrices works independently to characterize the territorial distribution of toxic compounds, without proving any correlated health risk for residents., Objectives: We propose a new biomonitoring model based on a whole systemic analytical evaluation of environmental context. The paradigm of the method consists of identifying the sources of pollution, the migration pathways of those pollutants and their effects on target organisms. By means of this innovative, holistic epidemiological approach, we included healthy human subjects in a cohort to identify potential risks of exposure and predict possible correlated clinical outcomes. 4205 residents of the Campania region were enrolled in the "SPES" biomonitoring study, which especially focused on the areas dubbed "Land of Fires" in the recent decades., Discussion: The analysis of environmental exposure risk suffers the lack of data integration from various science fields, and this comes down to a limited point of view and a limited knowledge of phenomena. In implementing our model, we first constructed an analytical picture of the Real-world situation. We next conducted a comparative risk assessment, in order to identify possible correlations between pollution and health within a holistic view., Conclusion: This type of research activities aims to support the implementation of public health interventions and to become a reference model in the evaluation of the risk of exposure to environmental pollutants., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

As of November 17, 2021, SARS-CoV-2 (Severe Acute Respiratory Syndrome CoronaVirus 2), the causative agent of COVID-19 (COronaVIrus Disease 19), has infected ~250 million people worldwide, causing around five million deaths. Titers of anti-SARS-CoV-2 neutralizing antibodies were relatively stable for at least 9 months in a population-based study conducted in Wuhan, China, both in symptomatic and in asymptomatic individuals. In the mass screening campaign conducted in the town of Ariano Irpino (Avellino, Italy) in May, 2020, 5.7% (95% CI: 5.3-6-1) of the 13,444 asymptomatic citizens screened were positive for anti-nucleocapsid antibodies against SARS-CoV-2. Among these, 422 citizens were re-tested for anti SARS-CoV-2 antibodies in January, 2021 and/or in April, 2021 and enrolled in this longitudinal observational study. Median (interquartile range) age of the study cohort was 46 years (29-59), with 47 (11.1%) participants of minor age, while 217 (51.4%) participants were females. There was no evidence of re-infection in any of the subjects included. Presence of anti-nuclear antibodies antibodies (Elecysis, Roche) was reported in 95.7 and 93.7% of evaluable participants in January and April, 2021. Multiple logistic regression analysis used to explore associations between age, sex and seroprevalence showed that adults vs. minors had significantly lower odds of having anti-S1 antibodies (Biorad) both in January, 2021 and in April, 2021. Our findings showed that antibodies remained detectable at least 11.5 months after infection in >90% of never symptomatic cases. Further investigation is required to establish duration of immunity against SARS-CoV-2., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Coppola, Buonerba, Cardinale, Lo Conte, Sansone, Rofrano, De Vita, Morgante, Triassi, Atripaldi, Brambilla, Sabatino, Pierri, Pacella, Pizzolante, Pierri, Ferrucci, Zollo, Capasso, Stringhini, Ascierto, Roperto and Cerino.)

Background: We aimed to test the hypothesis that the immune-modulatory effect of statins may improve survival outcomes in patients with non-muscle invasive bladder cancer (NMIBC). We focused on a cohort of patients diagnosed with high risk NMIBC, that were treated with intravesical BCG immunotherapy., Methods: We included patients at first diagnosis of T1 high grade NMIBC after transurethral resection of bladder (TURB). All procedures were performed at 18 different tertiary institutions between January 2002 and December 2012. Univariable and multivariable models were used to test differences in terms of residual tumor, disease recurrence, disease progression and overall mortality (OM) rates., Results: Overall, 1510 patients with T1 high grade NMIBC at TURB were included in our analyses. Of these, 402 (26.6%) were statin users. At multivariable analysis, statin use was associated with a higher rate of high-grade BC at re-TURB (OR: 1.37, 95%CI: 1.04-1.78; P=0.022), while at follow-up it was not independently associated with OM (HR: 0.71, 95%CI: 0.50-1.03; P=0.068) and disease progression rates (HR: 0.97, 95%CI: 0.79-1.19; P=0.753). Conversely, statin use has been shown to be independently associated with a lower risk of recurrence (HR:0.80, 95%CI: 0.67-0.95; P=0.009). The median recurrence-free survival was 47 (95%CI 40-49) months for those classified as non-statin users vs. 53 (95%CI 48-68) months in those classified as statin users., Conclusions: Statin daily intake do not compromise oncological outcomes in high risk NMIBC patients treated with BCG. Moreover, statin may have a beneficial effect on recurrence rates in this cohort of patients.

Prostate and bladder cancer represent the two most frequently diagnosed genito-urinary malignancies. Diet has been implicated in both prostate and bladder cancer. Given their prolonged latency and high prevalence rates, both prostate and bladder cancer represent attractive candidates for dietary preventive measures, including the use of nutritional supplements. Flavonols, a class of flavonoids, are commonly found in fruit and vegetables and are known for their protective effect against diabetes and cardiovascular diseases. Furthermore, a higher dietary intake of flavonols was associated with a lower risk of both bladder and prostate cancer in epidemiological studies. In this systematic review, we gathered all available evidence supporting the anti-cancer potential of selected flavonols (kaempferol, fisetin and myricetin) against bladder and prostate cancer. A total of 21, 15 and 7 pre-clinical articles on bladder or prostate cancer reporting on kaempferol, fisetin and myricetin, respectively, were found, while more limited evidence was available from animal models and epidemiological studies or clinical trials. In conclusion, the available evidence supports the potential use of these flavonols in prostate and bladder cancer, with a low expected toxicity, thus providing the rationale for clinical trials that explore dosing, settings for clinical use as well as their use in combination with other pharmacological and non-pharmacological interventions.

The objective of the current research was to explore the potential prognostic value of readily available clinical and pathologic variables in bladder cancer. The novel association found between cholesterol levels and prognosis may provide the rationale for exploring novel treatments. Patients included had histologically confirmed urothelial bladder cancer and were treated with at least 3 cycles of cisplatin-based neoadjuvant chemotherapy before radical cystectomy with lymphadenectomy. A total of 245 patients at low, intermediate and high risk, presenting with 0-1, 2 or 3-4 risk factors, including positive lymph nodes, Hb <12.8, NLR ≥2.7 and cholesterol levels ≥199, were included. Five-year cancer-specific survival rate was 0.67, 0.78 and 0.94 at high, intermediate and low risk, respectively. Total cholesterol levels at the time of cystectomy may represent a commonly assessable prognostic factor and may be incorporated in a clinically meaningful risk-group classification model.

Introduction: Metastatic castration-resistant prostate cancer (mCRPC) is a deadly disease. Enzalutamide is an oral second-generation anti-androgen that is active in mCRPC. Circulating tumor cells (CTC) count correlates with overall survival (OS) in mCRPC, whereas detection of the androgen-receptor splice variant 7 (AR-V7) in CTC predicts poor response to oral second-generation anti-androgens. Also, loss of PTEN (phosphatase and tensin homolog) in CTC is a biomarker of poor prognosis in mCRPC., Patients and Methods: In this translational study, we employed flow cytometry to assess total, PTEN - , and AR-V7 + CTC count per 7.5 mL of whole blood in a prospective cohort of patients with mCRPC receiving enzalutamide., Results: CTCs were assessed in a total of 45 men with mCRPC at baseline and at 12 weeks. Overall, CTC, PTEN - CTC, and AR-V7 + CTC detection rate was high, at baseline, with 84.4%, 71.1%, and 51.1% of samples showing at least 1 cell/7.5-mL blood, respectively, and after 3 months, with 93.3%, 64.4%, and 77.7% of samples showing at least 1 cell/7.5-mL blood, respectively. Median radiographic progression-free survival (rPFS) and OS were 6 (95% confidence interval [CI], 5.6-9) and 14.3 (95% CI, 12.8-20.3) months, respectively. Median (interquartile range) total CTC count at baseline was 5 (3; 8), whereas median (interquartile range) PTEN - CTC count was 2 (0; 4) and median (interquartile range) AR-V7 + CTC count was 1 (0; 3). At baseline, ≥ 5 versus < 5 total CTC count was associated with worse rPFS (hazard ratio [HR], 2.35; 95% CI, 1.14-4.84; P= .021) and OS (HR, 3.08; 95% CI, 1.45-6.54; P = .003), whereas ≥ 2 versus < 2 PTEN - CTC count was associated with worse rPFS (HR, 3.96; 95% CI, 1.8-8.72; P= .001) and OS (HR, 2.36; 95% CI, 1.12-5; P= .025). Finally, ≥ 1 versus < 1 AR-V7 + CTC count was also associated with worse rPFS (HR, 5.05; 95% CI, 2.4-10.64; P< .001) and OS (HR, 2.25; 95% CI, 1.1-4.58; P= .026)., Conclusions: Despite multiple limitations, including the small sample size, our preliminary study suggests that assessment of CTC via flow cytometry may provide potentially useful prognostic and predictive information in advanced prostate cancer. Further studies are warranted. Micro-Abstract: In this study, men with metastatic castration-resistant prostate cancer, scheduled to start enzalutamide, were assessed for circulating tumor cell count and molecular characterization (total, PTEN - , and AR-V7 + circulating tumor cell count) by the use of flow cytometry. We found that flow cytometry could be used to enumerate circulating tumor cells, but also to assess molecular biomarkers on their surface., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Molecular heterogeneity and availability of different therapeutic strategies are relevant clinical features of prostate cancer. On this basis, there is an urgent need to identify prognostic and predictive biomarkers for an individualized therapeutic approach. In this context, researchers focused their attention on biomarkers able to discriminate potential life-threatening from organ-confined disease. Such biomarker could provide aid in clinical decision making, helping to choose the treatment which ensures the best results in terms of patient survival and quality of life. To address this need, many new laboratory tests have been proposed, with a clear tendency to use panels of combined biomarkers. In this review we evaluate current data on the application in clinical practice of the most promising laboratory tests: Phi, 4K score and Stockholm 3 as circulating biomarkers, Mi-prostate score, Exo DX Prostate and Select MD-X as urinary biomarkers, Confirm MDx, Oncotype Dx, Prolaris and Decipher as tissue biomarkers. In particular, the ability of these tests in the identification of clinically significant PCa and their potential use for precision medicine have been explored in this review.

Aim: This study aims to investigate any modification of serological FSCN1 in prostate cancer patients compared with patients without neoplasia., Material & Methods: Clinical data and blood specimens from patients with and without prostate cancer were obtained. A quantitative sandwich ELISA method was used to determine serological values of FSCN1., Results: Although serum values of FSCN1 were dissimilar in the two cohorts of patients (6.90 vs 7.33 ng/ml), the difference was not statistically significant (p = 0.20). Serum values of FSCN1 stratified for Gleason score groups were not significantly distinguishable (p = 0.65). A negative correlation (rho = -0.331; p = 0.009) was reported between FSCN1 and age., Conclusion: Further studies are required to evaluate a possible diagnostic role of FSCN1 in prostate cancer., Competing Interests: Financial & competing interests disclosure This report was supported by George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, Romania, with funds from an internal competition. ‘Fascin an eventual new biomarker in prostate cancer’, is specified with a reference number (9/17800 of 22 December 2015). C Buonerba is a member of the Future Science OA Editorial Board. They were not involved in any editorial decisions related to the publication of this article, and all author details were blinded to the article’s peer reviewers as per the journal’s double-blind peer review policy. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript., (© 2021 The Authors.)

In this retrospective study, a cohort of 67 subjects vaccinated with AZD1222 was retrospectively observed. Consistently with published findings, no serious adverse event was reported, and all adverse events reported (fever, muscle ache and/or pain in the site of injection) had resolved by day 8. Of note, some citizens were prescribed low-dose aspirin and even heparin for thrombosis prevention. We also found variations in laboratory test results (full blood count and chemistry) on day 1 compared with day 8. Physicians should be aware that no prevention therapy for thrombosis is currently recommended, given the very low incidence of this side effect. Additional studies are warranted to interpret our findings., Competing Interests: Financial & competing interests disclosure The authors have no relevant affiliationsor financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript., (© 2021 The Authors.)

To identify host genetic determinants involved in humoral immunity and associated with the risk of developing severe COVID-19, we analyzed 500 SARS-CoV-2 positive subjects from Southern Italy. We examined the coding sequences of 10 common variable immunodeficiency-associated genes obtained by the whole-exome sequencing of 121 hospitalized patients. These 10 genes showed significant enrichment in predicted pathogenic point mutations in severe patients compared with the non-severe ones. Moreover, in the TNFRSF13C gene, the minor allele of the p.His159Tyr variant, which is known to increase NF-kB activation and B-cell production, was significantly more frequent in the 38 severe cases compared to both the 83 non-severe patients and the 375 asymptomatic subjects further genotyped. This finding identified a potential genetic risk factor of severe COVID-19 that not only may serve to unravel the mechanisms underlying the disease severity but, also, may contribute to build the rationale for individualized management based on B-cell therapy.

The Experimental Zooprophylactic Institute of Southern Italy (Istitituto Zooprofilattico Sperimentale del Mezzogiorno, IZSM) is a public health institution operating within the Italian National Health Service. Over the past 5 years [IZSM] has promoted several research studies and interventions in an effort to tackle the 'Land of Fires' phenomenon, caused by the continued trafficking and uncontrolled incineration of waste that has affected some areas of Campania for decades. In this article, a mathematical model that generates a municipality index of environmental pressure is presented. The model was developed by a multidisciplinary team led by an environmental engineer and included researchers in the fields of veterinary and human medicine, biology and computer science. This model may serve as a geostratification tool useful for the design of human biomonitoring studies, although it may also be employed for strategic planning of remediation programs and public health interventions., Competing Interests: Financial & competing interests disclosure Translation services were supplied by Translated S.r.l., funding of which was supported by Istituto Zooprofilattico Sperimentale del Mezzogiorno. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No further writing assistance was utilized in the production of this manuscript., (© 2021 Carlo Buonerba.)

Aim: To assess the value of bone scintigraphy and 18 F-fluorocholine PET/computed tomography (CT) in predicting outcome in patients with prostate cancer and bone metastases treated with 223 radium., Materials & Methods: Retrospective analysis of 48 patients that underwent 223 radium therapy. End points were pain relief and overall survival., Results: After therapy, pain relief was observed in 27 patients. Patients without pain relief had more bone lesions at PET/CT than at bone scintigraphy (pretherapy imaging mismatch). In 39 patients who completed treatment protocol, post-therapy alkaline phosphatase and pretherapy imaging mismatch were independent predictors of poor overall survival., Conclusion: Patients with more lesions at 18 F-fluorocholine PET/CT than at bone scintigraphy had a poor prognosis. The combined imaging approach could be useful to predict outcome after 223 radium therapy., Competing Interests: Financial & competing interests disclosure The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript., (© 2021 Alberto Cuocolo.)

Genome-wide association studies (GWAS) found locus 3p21.31 associated with severe COVID-19. CCR5 resides at the same locus and, given its known biological role in other infection diseases, we investigated if common noncoding and rare coding variants, affecting CCR5 , can predispose to severe COVID-19. We combined single nucleotide polymorphisms (SNPs) that met the suggestive significance level ( P ≤ 1 × 10 -5 ) at the 3p21.31 locus in public GWAS datasets (6406 COVID-19 hospitalized patients and 902,088 controls) with gene expression data from 208 lung tissues, Hi-C, and Chip-seq data. Through whole exome sequencing (WES), we explored rare coding variants in 147 severe COVID-19 patients. We identified three SNPs (rs9845542, rs12639314, and rs35951367) associated with severe COVID-19 whose risk alleles correlated with low CCR5 expression in lung tissues. The rs35951367 resided in a CTFC binding site that interacts with CCR5 gene in lung tissues and was confirmed to be associated with severe COVID-19 in two independent datasets. We also identified a rare coding variant (rs34418657) associated with the risk of developing severe COVID-19. Our results suggest a biological role of CCR5 in the progression of COVID-19 as common and rare genetic variants can increase the risk of developing severe COVID-19 by affecting the functions of CCR5 .

Soft-tissue sarcomas are rare tumors characterized by pathogenetic, morphological, and clinical intrinsic variability. Median survival of patients with advanced tumors are usually chemo- and radio-resistant, and standard treatments yield low response rates and poor survival results. The identification of defined genomic alterations in sarcoma could represent the premise for targeted treatments. Summarizing, soft-tissue sarcomas can be differentiated into histotypes with reciprocal chromosomal translocations, with defined oncogenic mutations and complex karyotypes. If the latter are improbably approached with targeted treatments, many suggest that innovative therapies interfering with the identified fusion oncoproteins and altered pathways could be potentially resolutive. In most cases, the characteristic genetic signature is discouragingly defined as "undruggable", which poses a challenge for the development of novel pharmacological approaches. In this review, a summary of genomic alterations recognized in most common soft-tissue sarcoma is reported together with current and future therapeutic opportunities.

Background: Three or four cycles of cisplatin-based chemotherapy is the standard neoadjuvant treatment prior to cystectomy in patients with muscle-invasive bladder cancer. Although NCCN guidelines recommend 4 cycles of cisplatin-gemcitabine, three cycles are also commonly administered in clinical practice. In this multicenter retrospective study, we assessed a large and homogenous cohort of patients with urothelial bladder cancer (UBC) treated with three or four cycles of neoadjuvant cisplatin-gemcitabine followed by radical cystectomy, in order to explore whether three vs. four cycles were associated with different outcomes., Methods: Patients with histologically confirmed muscle-invasive UBC included in this retrospective study had to be treated with either 3 (cohort A) or 4 (cohort B) cycles of cisplatin-gemcitabine as neoadjuvant therapy before undergoing radical cystectomy with lymphadenectomy. Outcomes including pathologic downstaging to non-muscle invasive disease, pathologic complete response (defined as absence of disease -ypT0), overall- and cancer-specific- survival as well as time to recurrence were compared between cohorts A vs. B., Results: A total of 219 patients treated at 14 different high-volume Institutions were included in this retrospective study. Patients who received 3 (cohort A) vs. 4 (cohort B) cycles of neoadjuvant cisplatin-gemcitabine were 160 (73,1%) vs. 59 (26,9%).At univariate analysis, the number of neoadjuvant cycles was not associated with either pathologic complete response, pathologic downstaging, time to recurrence, cancer specific, and overall survival. Of note, patients in cohort B vs. A showed a worse non-cancer specific overall survival at univariate analysis (HR= 2.53; 95 CI= 1.05 - 6.10; p=0.046), although this finding was not confirmed at multivariate analysis., Conclusions: Our findings suggest that 3 cycles of cisplatin-gemcitabine may be equally effective, with less long-term toxicity, compared to 4 cycles in the neoadjuvant setting., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ferro, de Cobelli, Musi, Lucarelli, Terracciano, Pacella, Muto, Porreca, Busetto, Del Giudice, Soria, Gontero, Cantiello, Damiano, Crocerossa, Farhan, Autorino, Vartolomei, Muto, Marchioni, Mari, Scafuri, Minervini, Longo, Chiancone, Perdona, De Placido, Verde, Catellani, Luzzago, Mistretta, Ditonno, Caputo, Battaglia, Zamboni, Antonelli, Greco, Russo, Hurle, Crisan, Manfredi, Porpiglia, Di Lorenzo, Crocetto and Buonerba.)

The onset of the new SARS-CoV-2 coronavirus encouraged the development of new serologic tests that could be additional and complementary to real-time RT-PCR-based assays. In such a context, the study of performances of available tests is urgently needed, as their use has just been initiated for seroprevalence assessment. The aim of this study was to compare four chemiluminescence immunoassays and one immunochromatography test for SARS-Cov-2 antibodies for the evaluation of the degree of diffusion of SARS-CoV-2 infection in Salerno Province (Campania Region, Italy). A total of 3,185 specimens from citizens were tested for anti-SARS-CoV-2 antibodies as part of a screening program. Four automated immunoassays (Abbott and Liaison SARS-CoV-2 CLIA IgG and Roche and Siemens SARS-CoV-2 CLIA IgM/IgG/IgA assays) and one lateral flow immunoassay (LFIA Technogenetics IgG-IgM COVID-19) were used. Seroprevalence in the entire cohort was 2.41, 2.10, 1.82, and 1.85% according to the Liaison IgG, Abbott IgG, Siemens, and Roche total Ig tests, respectively. When we explored the agreement among the rapid tests and the serologic assays, we reported good agreement for Abbott, Siemens, and Roche (Cohen's Kappa coefficient 0.69, 0.67, and 0.67, respectively), whereas we found moderate agreement for Liaison (Cohen's kappa coefficient 0.58). Our study showed that Abbott and Liaison SARS-CoV-2 CLIA IgG, Roche and Siemens SARS-CoV-2 CLIA IgM/IgG/IgA assays, and LFIA Technogenetics IgG-IgM COVID-19 have good agreement in seroprevalence assessment. In addition, our findings indicate that the prevalence of IgG and total Ig antibodies against SARS-CoV-2 at the time of the study was as low as around 3%, likely explaining the amplitude of the current second wave., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Cerino, Gallo, Pierri, Buonerba, Di Concilio, Cuomo, Vassallo, Lo Conte, Coppola, Pizzolante, Boccia, Ferrucci, Atripaldi, Triassi, Pacella, Cennamo, Romano, Sorbo, Furno, Catapano, Contina, Perruolo, D'Amora, Terracciano and Portella.)

The established risk factors of coronavirus disease 2019 (COVID-19) are advanced age, male sex, and comorbidities, but they do not fully explain the wide spectrum of disease manifestations. Genetic factors implicated in the host antiviral response provide for novel insights into its pathogenesis. We performed an in-depth genetic analysis of chromosome 21 exploiting the genome-wide association study data, including 6,406 individuals hospitalized for COVID-19 and 902,088 controls with European genetic ancestry from the COVID-19 Host Genetics Initiative. We found that five single nucleotide polymorphisms within TMPRSS2 and near MX1 gene show associations with severe COVID-19. The minor alleles of the five single nucleotide polymorphisms (SNPs) correlated with a reduced risk of developing severe COVID-19 and high level of MX1 expression in blood. Our findings demonstrate that host genetic factors can influence the different clinical presentations of COVID-19 and that MX1 could be a potential therapeutic target., Competing Interests: The authors declare that there are no competing interests., (© 2021 The Authors.)